Activation of the stress axis is present in a number of patients with depression. In addition alterations in brain opioid receptors in depressed patients has been found by brain imaging. Both stress hormones and opioid receptors are involved in the regulation of reproductive axis hormones. In this study, we are interested in the links between these two biological systems and treatment response to a standard antidepressant, fluoxetine, and the effects of estrogen in altering the response to antidepressants. At baseline we will evaluate the stress axis with the use of metyrapone, and examine brain opioid receptors with [11C]-carfentanil by PET imaging. Following these studies, women will be enrolled in a 6 week trial of fluoxetine At the end of 6 weeks, individuals who have not fully responded to treatment, will be randomized to receive either estrogen augmentation or placebo for an additional 4 weeks.